Management of patients with glioblastoma (GBM) remains challenging. Prognosis is quite poor with a median survival of less than one year in the setting of recurrent disease after tumor resection and standard chemoradiation. As GBM is typically characterized by marked angiogenesis mediated by vascular endothelial growth factor (VEGF), significant interest has been generated towards targeting VEGF. While anti-angiogenic agents such as bevacizumab (which is targeting VEGF signaling) has been promising and increasingly used in this patient population, assessment of radiographic response with this class of agents has been difficult due to their unique effects on the tumor vasculature. Specifically, diminished contrast enhancement as it can be seen with standard post-treatment magnetic resonance imaging (MRI) may not necessarily correspond to reduction in viable tumor after administration of VEGF-targeting agents, a phenomenon called pseudo-response. Moreover, not all patients demonstrate clinical benefit from anti-angiogenic therapies, why the development of novel and reliable imaging biomarkers of treatment response in this patient population would address a major unmet need and improve patient management. Based on an NIH-funded prospective clinical trial performed by the Radiation Therapy Oncology Group in collaboration with American College of Radiology Imaging Network (RTOG 0825/ACRIN6677) we have strong evidence to suggest that proton magnetic resonance spectroscopic imaging (1H MRSI) can reliably identify early tumor recurrence in GBM patients. We speculate that the main advantage of using MRS is based on the ability to monitor cellular tumor metabolism, a feature considered independent of the state of tumor- related angiogenesis and vascularity. Specifically, MRS measures choline (Cho), a marker for accelerated membrane synthesis that occurs in rapidly dividing cancer cells and N-Acetylaspartate (NAA), a marker for neuronal integrity, which is compromised in tumor progression. Recent studies have shown that changes in NAA/Cho at 8 weeks post anti-angiogenic treatment were predictive of six-month progression-free survival and overall survival. Based on these studies, we hypothesize that a significant decline in the NAA/Cho ratio after bevacizumab treatment is predictive of early treatment failure. To consolidate these findings, we propose to validate the application of 1H MRSI in two cohorts: 1) in patients receiving bevacizumab monotherapy, and 2) in patients treated with bevacizumab-based chemotherapy. 3T MRI and MRSI will be performed before initiation of anti-VEGF therapy and at predetermined time points during treatment. Validation of MRS as a powerful imaging biomarker of treatment response in glioma patients treated with anti-angiogenic based therapies would add an effective tool to select patients to better therapies, save costs and overall improve patient management.